oa Screening for novel natural and synthetic inhibitors for human α-amylases and their structure determination: An effective approach to control diabetes mellitus and obesity

Background: Non-insulin-dependent diabetes mellitus (NIDDM) is one of the most common adult diseases caused by a secretory decrease in insulin from pancreatic Langerhans cells and/or peripheral cells which become resistant to the action of insulin as in the case of obesity. Serious side effects such as retinopathy, neuropathy, and cataracts are also brought about by its long-term manifestation. At present, the direct clinical therapy in NIDDM is to optimize or control the postprandial blood glucose (PBG) level. Polysaccharide degrading enzyme, such as α-amylase catalyzes the cleavage of starch to produce glucose and other smaller polysaccharides which leads to an increase of the glucose level in the blood. Thus, the retardation of the action of this enzyme by suitable inhibitors may be one of the most effective approaches to control NIDDM. Objectives: The aim of this work was to screen, isolate and determine the structure of novel inhibitors for human polysaccharide degrading enzymes, salivary and pancreatic α-amylases, using natural resources and synthetic compounds. Methods: We prepared the total extracts of several herbs and plants collected from different locations in Egypt and in Qatar randomly and based on traditional use. Each extract was assayed for potential amylase inhibitors. The potential inhibitors were isolated using silica gel chromatography. The structure of each inhibitor was determined using elemental analysis, IR, 1H-NMR, MS and 13C-NMR. Hundreds of synthetic compounds have also been tested for inhibition capabilities. Results: Our study demonstrated that the total extract of four plants showed a significant inhibition of human saliva and pancreatic α-amylases. The active compounds from two plants were isolated and their structures determined. Three synthetic compounds with a significant but variable degree of inhibition of human saliva α-amylase and pancreatic amylase were identified. Conclusion: The novel inhibitors isolated in this study could form the basis for clinical trials to demonstrate the effectiveness of these compounds in lowering the glucose level in NIDDM patients and obese people.